1. Field of the Invention
This invention relates to chemical analysis of liquids, and more particularly, to an optical sensor for sensing analyte content of biological fluids such as blood.
2. Background Information
Chemical analysis of liquids, including biological fluids such as blood, plasma or urine is often desirable or necessary. Sensors that utilize various analytical elements to facilitate liquid analysis are known. These sensing elements have often included a reagent in either a wet or dry form sensitive to a substance or characteristic under analysis, termed analyte herein. The reagent, upon contacting a liquid sample containing the analyte, effects formation of a colored material or another detectable change in response to the presence of the analyte. Examples of dry analytical sensing elements include pH test strips and similar indicators wherein a paper or other highly absorbent carrier is impregnated with a material, chemically reactive or otherwise, that responds to contact with liquid containing hydrogen ion or other analyte and either generates color or changes color. Specific examples of such test strips are disclosed in European publication No. EP 0119 861 B1, which describes a test for bilirubin; in U.S. Pat. No. 5,462,858 which describes a dry multilayer strip for measuring transaminase activity; and U.S. Pat. No. 5,464,777 which discloses a reflectance based assay for creatinine. While providing a convenience factor, in that they can be stored dry and are ready to use on demand, these individual test elements are generally utilized in "wet" blood or serum chemistry, wherein the strips become saturated during use. This hydration and the depletion of reactive chemical reagents effectively prevents their re-use. This aspect also complicates handling and disposal of the multitude of individual used test elements.
Alternatively, some analytes can be measured with a sensing element which is used repeatedly after an initial wet-up and calibration and with washes between samples. For example a reuseable electrochemical sensor for oxygen is described in commonly assigned U.S. Pat. No. 5,387,329 and a reuseable electrochemical sensor for glucose is described in commonly assigned U.S. Pat. No. 5,601,694. These sensors function within the context of a complex piece of support instrumentation to perform the repetitive calibration and wash functions.
Other analytical sensing elements which are based on an optical signal response are disclosed in U.S. Pat. Nos. 4,752,115; 5,043,286; 5,453,248 and by Papkovsky et al in Anal. Chem. vol 67 pp 4112-4117 (1995) which describe an oxygen sensitive dye in a polymer membrane, as does commonly assigned U.S. patent application Ser. No. 08/617,714, now U.S. Pat. No. 5,863,460 which is hereby incorporated in its entirety, herein. Examples of an optical CO.sub.2 sensor are described in U.S. Pat. Nos. 4,824,789; 5,326,531 and 5,506,148. These elements utilize a polymer based membrane chemistry to achieve advantages in storage, and continuous use or re-use as compared to the wetable or hydrated single use chemistry strips. Analytical elements of this type are typically adapted for multiple uses within a single sample chamber of an optical sensor assembly. In operation, a fluid sample of unknown analyte content (an "unknown sample") is tested by inserting the sample into the sample chamber where it contacts the analytical element. A change in the optical properties of the analytical element is observed. Such an observation is then compared to calibration data previously obtained by similarly testing a calibration liquid of known analyte content. In this manner, characteristics of the analyte of interest in the unknown sample are determined.
An example of a single use optical sensor application of this normally reuseable type is known as a "AVL OPTI 1" available from AVL List GmbH of Graz, Austria. While sensors of this type may operate satisfactorily in many applications, they are not without limitations. In particular, they rely on sequential steps for calibration and subsequent sample readings, in which each such sensing device must be individually calibrated prior to testing an unknown sample. This technique is required due to variations in analytical elements from sensor to sensor. These variations may be attributed to a variety of factors, including manufacturing variables such as differences in individual lots, and distinct storage histories.
Sequential calibration and sample reading may problematically lead to sample contamination in the event the sample chamber and analytical elements are insufficiently washed between samples. In addition, the calibration is time consuming and may delay analysis of the unknown sample. This delay may be particularly inconvenient in some operating environments such as, for example, critical care facilities.
An additional disadvantage of the sequential approach is the temporal variation or time delay between testing of the calibrant and testing of the unknown sample. This variation may provide a potential opportunity for inaccuracies in test results.
Further, discarded wash fluid comprises approximately 80% of the waste generated by such conventional sensor based testing techniques. This waste is classified as biohazardous particularly if it is co-mingled with biological samples and thus disposal thereof is relatively expensive, both in economic and environmental terms. This waste also poses a potential health risk to health care workers and those who may otherwise come into contact with the waste during or after disposal.
Thus, a need exists for an improved optical sensor that eliminates the need for serial calibration and addresses the problems of waste generation inherent in sensor practices of the prior art while retaining the advantages of disposable, use on demand, devices.